The principal aim of the project is an understanding of the molecular basis of inherited human anemias, known as thalassemia syndromes. The work specifically involves an analysis of the structure of human hemoglobin genes from both normal and thalassemic individuals. Restriction enzyme mapping methods are first employed to define the presence, number, and gross architecture of the globin genes in various settings. Recombinant DNA cloning techniques are then utilized to isolate the genes in pure form for more detailed analysis by electron microscopy and DNA sequencing techniques. We hope that detailed analysis of this kind will lead to the characterization of specific mutations affecting hemoglobin genes in these disorders. An understanding of these mutations should shed considerable light on the signals within normal genes responsible for proper gene expression in man.